In a recent study of the brain’s waste disposal system, researchers at the University of Washington in St. Petersburg, Louis, in collaboration with investigators at the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), found that between the brain and its tough protective covering, the dura mater. discovered a direct connection. These links can allow waste fluid to leave the brain and expose the brain to immune cells and other signals coming from the dura. This challenges conventional wisdom which has suggested that the brain is isolated from its surroundings by a series of protective barriers, protecting it from dangerous chemicals and toxins lurking in the environment.
Waste fluid moves from the brain to the body like sewage exits our homes. In this study, we asked the question what happens once the ‘drain pipe’ leaves the ‘house’-; In this case, brain-; and connects the body with the city’s sewer system.”
Daniel S. of the NINDS. Rich, MD, Ph.D
Richer’s group collaborated with Professor Jonathan Kipnis’s lab at the University of Washington in St. Petersburg. Louie.
Reich’s lab uses high-resolution magnetic resonance imaging (MRI) to observe the connection between the human brain and the body’s lymphatic system. Meanwhile Kipnis’ group was independently using live-cell and other microscopic brain imaging techniques to study these systems in mice.
Using MRI, the researchers scanned the brains of a group of healthy volunteers who received injections of gadobutrol, a magnetic dye used to visualize blood brain blockages or other types of damage to blood vessels. Large veins are known to pass through the arachnoid barrier carrying blood from the brain, and these were clearly observed on MRI scans. As the scan progressed, a ring of dye appeared around the large veins that slowly spread over time, suggesting that fluid could pass through the space around the large veins where they cross the arachnoid barrier on their way to the dura.
Kipnis’ lab was making similar observations in mice. His team injected mice with light-emitting molecules. As with MRI tests, fluid containing these light-emitting molecules has been shown to slip through the arachnoid barrier where blood vessels pass.
Together, the labs found a “cuff” of cells surrounding the blood vessels as they pass through the arachnoid space. These areas, called arachnoid cuff exit (ACE) points, act as places where fluid, molecules, and even some cells can pass from the brain to the dura and vice versa, without allowing complete mixing of the two fluids. In some disorders, such as Alzheimer’s disease, impairment of waste clearance can produce disease-causing proteins. Continuing the sewer analogy, Kipnis explained the possible connection of ACE points:
“If your sink is clogged, you can remove the water from the sink or fix the faucet, but eventually you have to fix the drain,” he said. “In the brain, clogs at ACE points can prevent waste from getting out. If we can find ways to clear these clogs, we can protect the brain.”
An implication of ACE points is that they are areas where the immune system can unfold and react to changes occurring in the brain. When Dr. in rats. In a disorder where the immune system attacks the myelin of the brain and spinal cord, Kipnis’s lab found immune cells around ACE points and even in blood vessel walls and cuff cells; This leads to the ACE point itself breaking down over time. When the ability of immune cells to directly interact with ACE points was blocked, the severity of the infection was reduced.
“The immune system uses molecules to communicate from the brain to the dura mater,” Kipnis said. “This crossing needs to be tightly regulated, otherwise detrimental effects on brain function can occur.”
Reich and his team also observed an interesting connection between participants’ age and leakage of ACE points. In older participants, more dye leaked into the fluid and space around the blood vessels.
“This may point to a slower breakdown of ACE points with aging,” Reich said, “and this may result in the brain and immune system now communicating in ways they’re not supposed to.”
The association with aging and disruption of the barrier separating the brain and immune system fits with what has been observed in aging mice and autoimmune disorders such as multiple sclerosis. This new link between the brain and the immune system may help explain why our risk of developing neurodegenerative diseases increases as we age, but more research is needed to confirm this link.
This research was supported by the NINDS Intramural Research Program, the National Institute on Aging (AG034113, AG057496, AG078106) and the Cure Alzheimer’s Fund BEE Consortium.
Smith, LCD, etc (2024). Identifying a direct connection between the dura and the brain. the nature. doi.org/10.1038/s41586-023-06993-7.